Parkinson disease (PD) is the second most prevalent neurodegenerative disease and affects more than one million elderly Americans. As the population ages, the burden of PD is expected to increase. Although there are effective measures to control the symptoms of PD, patients eventually develop severe physical and mental disabilities and often die of complications. My research aims to ascertain the environmental and genetic causes of PD and to characterize high risk populations through research on nonmotor symptoms and biomarkers. I currently have three ongoing projects to accomplish these goals. Parkinson's Genes and Environment (PAGE) Study: The PAGE study was built within a large prospective cohort that was initially established for cancer research. The cohort had collected extensive dietary and lifestyle data from approximately 0.5 million US older adults in mid-1990s. In this study, we have successfully collected genetic material from approximately 1,100 PD patients and 1,900 controls, and majority of them also provided additional exposure information that was not available from the cohort's baseline survey. This study has reported several important findings: 1) smoking duration, rather than intensity, is important in explaining the smoking-Parkinson relationship (Neurology, 2010);2) depression (Mov Disord 2010) and longer daytime napping (Am J Epidemiol, 2011) may be among the early nonmotor symptoms of PD;3) higher physical activity may lower the risk for PD (Neurology, 2010);and 4) diabetes may increase the risk for PD (Diabetes Care, 2011). Finally, in collaboration with others, we contributed to the identification of multiple genetic loci that were associated with PD risk (Nat Genetics, 2009, Lancet 2011, and PLoS Genetics 2011). The Shanghai Parkinson Study (SPS): The SPS is also being built based on a large prospective cohort - the Shanghai Women's Health Study (SWHS). The study is important because little PD research has been conducted among women, and the SWHS collected biospecimen at its baseline in 1997-2000. In this study, we aim to identify and clinically confirm Parkinson patients and to examine potential risk factors and early biomarkers for PD among women. We carried out a pilot in the late spring of 2010 and started main data collection this year which may last for several years. Parkinson Research in the Atherosclerosis Risk In Communities (ARIC) Study: The ARIC study is one of the most successful community-based cohort studies on cardiovascular research. The cohort was established in late 1980s and recruited over 15,000 participants, ages 45-64, from four US communities. With multiple cohort-wide blood collections, rich exposure data, numerous ancillary studies, more than 20 years of follow-up, and ongoing cognitive assessment, the ARIC cohort is an excellent resource for Parkinson research. We therefore plan to confirm PD cases and thus initiate a long-term Parkinson study in this well-established cohort. There will be two major aims of PD research in this cohort 1) to examine genetic and environmental risk factors for PD;2) to examine preclinical nonmotor symptoms of PD. In addition, my group is also working on a few other projects in collaboration with intra- and extramural investigators to search for causes of PD and other neurodegenerative diseases. Collaborators are from the Harvard University (the Health Professionals Follow-up Study, the Nurses Health Study, the Cancer Prevention Study II Nutrition Cohort), NIHES (the Agricultural Health Study and the Sister Study), and the Karolinska Institutet in Sweden (national-wide patient register).